Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168363/1/bju15289.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168363/2/bju15289_am.pd

Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168363/1/bju15289.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168363/2/bju15289_am.pd

Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE: We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION: NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS: Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS: Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY: There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer

Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer

© 2022 Springer Nature Switzerland AG. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1007/s00345-022-04160-7PurposeCisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin-ineligible. The aim of this study was to compare clinical outcomes after ≥3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis).  Methods We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN+M0) gem-carbo or gem-cis followed by RC. Results We included 747 patients treated with gem-carbo (n=147) or gem-cis (n=600). Patients treated with gem carbo had a higher Charlson Comorbidity Index (p=0.016) and more clinically node-positive disease (32% 88 versus 20%; p=0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p=0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR: 0.99 [95%CI, 0.61-1.59]; p=0.96), overall survival (OS) (HR: 1.20 91 [95%CI, 0.85-1.67]; p=0.31), or cancer-specific survival (CSS) (HR: 1.35 [95%CI, 0.93-1.96]; p=0.11). Median  OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6)(p=0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached)(p=0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. 4 Conclusion Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥3 cycles and undergo RC.Peer reviewe

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort

Purpose:While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort.Materials and Methods:We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival.Results:Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P <.001 and P <.01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P <.01 and P <.05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1).Conclusions:In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort

© 2023 by American Urological Association Education and Research, Inc. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1097/JU.0000000000003193Purpose: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. Materials and Methods: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. Results: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P Conclusions: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.Peer reviewe

The prognostic value of the neutrophil-to-lymphocyte ratio in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy

The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC

Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE: We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION: NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and </=pT1N0 stages. RESULTS AND LIMITATIONS: Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and </=pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS: Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY: There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer